Project Summary Work capacity is an important predictor of declining health or physical function, and of mortality, and is commonly measured as peak oxygen consumption. Peak oxygen consumption is very low in individuals with Down syndrome, the most prevalent genetic cause of intellectual disability. Previous research suggests individuals with Down syndrome may experience a double disadvantage when they are exercising: they may not be able to increase cardiac output sufficiently and they may not be able to allocate adequate blood flow to the working muscles. The overall aim of this research proposal is therefore to determine the impact of limitations in central and peripheral regulation of blood flow on work capacity in individuals with DS. We aim to examine both acute and chronic exercise responses to better understand the underlying mechanisms and the potential to improve health by using this knowledge in interventions. The candidate, Dr. Thessa Hilgenkamp, has a strong background in epidemiological research on health in individuals with intellectual disabilities including Down syndrome. Her research focuses on the benefits of physical activity and exercise in this population, and she has shown great potential to become a successful independent researcher in this field. Recently she has developed expertise in measuring autonomic regulation during exercise with Dr. Bo Fernhall in the Integrative Physiology Laboratory of the University of Illinois at Chicago. Her long-term goal is to improve the health of individuals with Down syndrome across the life span, by fully understanding autonomic dysfunction and cardiovascular regulation of the response to exercise and implementing this knowledge in physical activity and exercise interventions. Her short-term career goals are first to become a skilled, knowledgeable expert on cardiovascular exercise physiology and autonomic function in individuals with Down syndrome, and second to become a high-potential researcher in this specific field, both from the perspective of academia and from the perspective of clinical practice and the Down syndrome support networks in the community. This Career Development Award will allow her to receive additional training in technical knowledge and skills that will be in line with and complementary to the research proposal, to conduct research projects in collaboration with clinical practice and the Down syndrome support networks in the community, and to develop transferable skills necessary to become a successful independent researcher, such as grant writing, lab management and mentoring. Her mentor is Dr. Bo Fernhall, a world-renowned expert on cardiovascular exercise physiology and Down syndrome, and she will also be supported by Dr. Tracy Baynard and Dr. Philip Clifford of the Department of Kinesiology and Nutrition of the University of Illinois at Chicago. This Department is committed to Dr. Hilgenkamp's academic development and provides her with all the facilities she needs, including the equipment in the Integrative Physiology Laboratory that she needs. She also has the support of parent networks and the Special Olympics Illinois to conduct this research.